1. Alpha rat atrial natriuretic peptide (Alpha-RANP, atriopeptin III), the major circulating form of ANP's, inhibits pressor responses to angiotensin II, vasopressin, norepinephrine (NE) and clonidine when bolus-injected into the pithed rat. 2. A single bolus injection of Alpha-RANP does not alter the acute pressor Alpha-1-adrenoceptor mediated responses to sympathetic stimulation and phenylephrine. Neither does ANP appear to affect plasma NE concentration during stimulation or administration of NE. 3. Acute Alpha-1-mediated responses are also resistant to calcium channel blockers (e.g. nifedipine) whereas Alpha-2-mediated responses to NE or to clonidine, as well as those to angiotensin II and to vasopressin, are dependent on extracellular calcium and blocked by nifedipine. 4. Later phases of all pressor responses become more dependent on calcium flux and are similarly blocked by nifedipine and Alpha-RANP. 5. This pattern of Alpha-2-adrenoceptor specificity during acute pressor responses is not shared by a general vasodilator, sodium nitroprusside, which equally inhibits acute Alpha-1- and Alpha-2-mediated responses. 6. Constant infusion of Alpha-RANP into pithed rat inhibits Alpha-1-mediated pressor responses to sympathetic stimulation and also decreases stimulation-induced NE release. 7. It appears that in vascular tissue the noradrenergic neuroeffector function is relatively unavailable to bolus-injected Alpha-RANP but the presynaptic neuronal release of NE becomes diminished when exposed to longer term infusion of the peptide. 8. Mechanisms of antipressor action of Alpha-RANP appear to involve extracellular calcium flux in both the presynaptic neurone and the vascular smooth muscle.